(1) Field of the Invention
The present invention relates to an improved regenerated cellulose membrane to be used for an artificial organ and the like and a process for the preparation thereof. More particularly, the present invention relates to a regenerated cellulose membrane having an improved blood compatibility, and a process for the preparation thereof.
(2) Description of the Related Art
Recently, rapid progress has been made in the development of artificial organs such as an artificial kidney and an artificial lung, and in a plasma-separating apparatus and as is well-known, especially in hemodialysis therapy, a regenerated cellulose membrane, particularly a cuprammonium regenerated cellulose membrane, is widely used. Together with the development of dialysis apparatuses or dialysis techniques, the regenerated cellulose membrane has made great contributions to the survival and rehabilitation of patients with end-stage renal disease. This importance of the regenerated cellulose membrane is due to the excellent dialysis performance, high mechanical strength, and high safety level thereof obtained in practical use over many years.
Nevertheless, in spite of the progress made in hemodialysis therapy, many problems concerning the dialysis still remain. For example, the problem of a side effect stemming from a long-period administration of a large quantity of an anti-coagulant and as has been pointed out, if hemodialysis using a regenerated cellulose membrane or a certain other kinds membrane is carried out, a transient reduction of leukocytes or activation of the complement occurs. The relationship between the latter phenomena and the clinical symptoms, or the clinical significance, has not been clarified, but there is obviously a need to provide a regenerated cellulose membrane capable of moderating these phenomena without an adverse affect on the excellent dialysis performances of the regenerated cellulose membrane mentioned above.
Membranes composed of synthetic polymers have been proposed to moderate the above problems or phenomena, but these membranes themselves have problems in that they have a poor mechanical strength and is very susceptible to the formation of pinholes, it is difficult to sterilize because of a low heat resistance, and is difficult to apply because the properties thereof are not well-balanced, that is, a good balance cannot be maintained between the amount of water permeability and the amount of substance permeability.
Various methods have been proposed for improving the blood compatibility in regenerated cellulose membranes. For example, U.S. Pat. No. 3,616,935 proposes a method in which the surface of a membrane is modified with heparin to impart an anti-thrombus property to the membrane. However, the effect attained is not satisfactory and the cost is high. Another method has been proposed in which the surface of a regenerated cellulose membrane is coated with a polymer or a vitamin. However, the coating stability is unsatisfactory or sterilization is difficult. European Patent No. 155,534 proposes a method in which a regenerated cellulose membrane is reacted with an isocyanate prepolymer, and DE 334,113 proposes a method in which a polymer acid is chemically bonded to a regenerated cellulose membrane through a bridging agent. These methods, however, are unsatisfactory in that the reactants have a poor stability and the reaction steps are complicated. European Patent No. 172,437 (U.S. Pat. No. 4,668,396) proposes a dialysis membrane formed by using a modified cellulose such as diethylaminoethyl cellulose. However, the improvement in the effect of moderating the coagulation of blood is not satisfactory.